This invention relates to the preparation of 2'-deoxy-5-fluorouridine derivatives useful as antitumor medicines or intermediates thereof, and more particularly to the preparation of 2'-deoxy-3',5'-diacyl-5-fluorouridines from 2'-deoxyuridine via a novel intermediate compound.
2'-Deoxy-5-fluorouridine is a compound synthesized for use as an antitumor medicine, but actually this compound is high in toxicity and low in activity in the human body. To reduce toxicity and enhance antitumor activity, 2'-deoxy-5-fluorouridine derivatives such as 3',5'-diacyl derivatives (e.g. JP-A 58-49315) and 3-aroyl-3',5'-diacyl derivatives (e.g. JP 62-47197) have been developed. These derivatives are synthesized by acylating 2'-deoxy-5-fluorouridine by reaction with an acyl halide.
At present, however, 2'-deoxy-5-fluorouridine is very expensive and is not readily available because no industrially favorable method for the preparation of this compound has been developed.
Known processes of preparing diacyl derivatives of 2'-deoxy-5-fluorouridine include reducing a 2'-halogen derivative (JP 55-40598) and reacting fluorine gas with a diacyl derivative in an organic solvent (DDR Pat. No. 95001). However, the reduction process entails several steps to prepare the 2'-halogen derivative, and the fluorination in organic solvent is not easy to accomplish on an industrial scale.